This web page was produced as an assignment for an undergraduate
course at Davidson College.

Is there a gene for genius?

Can you imagine a world where intelligence could be genetically
controlled? With one gene? In the September 1999 edition of Nature,
Ya-Ping Tang et al. write, "Our results suggest that genetic
enhancement of mental and cognitive attributes such as intelligence and memory
in mammals is feasible". What!? A gene that can make you smarter! Below
is a detailed summary of what Tang et al. found and discussion on
the popular article in Time
about a week and a half later.

The Scientific Press

The researchers in Nature used Hebb's rule as a start
when looking for this gene. According to Hebb's rule (1949) "learning and
memory are based on modifications of synaptic strength among neurons that are
simultaneously active" (Tang et al., 1999). This phenomenon is
called synaptic plasticity and is a major component when building memories and
edifying knowledge.

Tang and his colleagues made two strains of transgenic mice
which overexpressed the NMDA (N-methyl-D-aspartate) receptor, namely the NR1-NR2B
variation. The receptor is heteromeric membrane protein with a subunit 1 (NR1)
and subunit 2 (NR2) which has four different variations, NR2A-D. The receptor
is a "synaptic coincidence detector, acts as a graded switch for memory
formation...and is critical in gating the age-dependent threshold for plasticity
and memory formation" (Tang et al., 1999). The receptor is a transmembrane
channel for Ca2+ but only works when glutamate from another cell binds (on the
NR2B subunit) and it receives an electric current from its own cell, thus the
pre- and post- synaptic neurons must both give a signal. The researchers used
CaM-kinase-II promoter which overexpressed the receptor in the cortex, striatum,
amygdala and the hippocampus of the transgenic mice (which they depicted nicely
with Western blots and in situ hybridization). These areas of the brain
play very important roles in memory formation. Tang also says that the mice
were healthy and fertile with no seizures or convulsions. This point is mentioned
in Time (since Ca2+ overload can lead to cell death--which is what
happens in during a stroke. The lack of oxygen stimulates overproduction of
glutamate which overwhelms the cell with calcium).

The researchers first set out to learn the nature of the receptor.
Using neurons in vitro, they induced charge and added glutamate to measure the
total charge transfer between two cells. They found the transgenic mice's charge
to be four times higher after 18 days than wild-type's. The results show that
the transgenic mice's plasticity remained high over time, at juvenile levels+.
NR2B is the most frequent subunit of NR2 found in juvenile development, which
explains why younger organisms tend to have a higher threshold for learning
and plasticity in memory. As we age, the NR2B subunits get replaced with NR2A
units and our plasticity gets worse. Hence, the older you are the more you forget
things; your neurons don't make the connections as fast. However, mice overexpressing
NR2B maintain the youthful level of long-term potentiation (LTP) and learn and
remember things better over time. The mice in which the NR2B subunit was overexpressed
performed significantly better on memory tests than their wild-type companions.
The tests measured emotional learning with fear-extinction paradigms, spatial
learning with a hidden-platform water maze, and visual recognition memory with
novel versus old objects.

The results clearly show that NR2B does help with LTP and memory
in mice. As memory is an integral part of intelligence, it is fair to conclude
that these mice were smarter. However, how testing the memory of mice with fear
paradigms and spatial tests correlates with the complexity and vast scope of
human memory is the point of consternation.

The Popular Press

The Time article came out September 13, 1999, just
eleven days after the article appeared in Nature. The cover sensationalized
the current implications and aura of the research; and although I think Time
did an satisfactory job in covering the gist of the research and in not overdramaticizing
it too much, people remember the cover and not so much the words of a five page
article. The hype was not so much about the receptor and what it does but the
potential of what it could be used to do. Though Time considered all
the other genes and their potential in the complexity of intelligence, they
didn't really question how this gene in effecting LTP and plasticity really
helps overall "IQ," as they so aptly titled the cover. The article
discussed few of the ethical and social issues surrounding it, comparing its
potential volatileness with The Bell Curve by Richard Herrnstein and
Charles Murray, gave some background information, and did not expound on the
gene NR2B. The huge issue left out was the ethics of gene therapy, which is
discussed below. Although, Lemonick makes it a point to write that intelligence
obviously involves many genes and not just this one, he creates the mindset
that Tang et al. most likely found a good one and one necessary for
high IQ. The article then does a spin on how "memory is absolutely crucial
to our consciousness," which is true. The article mentions the man H.M.
who in 1953 had surgery for epilepsy and had his hippocampus removed. H.M. could
not form new memories from that day on. The article also explained the essence
of memory and how there are systems of memory. For example,
Lemonick mentions basal ganglia as crucial to learning new motor skills and
the amygdala as crucial to recalling memories tied to emotion, and the medial
temporal lobe and hippocampus as crucial for forming and retaining short term
memories.

Lemonick explains the Tang et al. research, as far
as pertaining to their findings, well for a non-science article. He sufficiently
explains from plasticity and the process of how the receptor is turned on to
the phenomenon of long-term potentiation which, in general, is the formation
of memory. However, he doesn't even begin to discuss the NR2B receptor until
the very last page! Another sensationalized and controversial element is the
discussion of the future "therapeutic promise" that the article boasts.
Time seems to create the visage that this gene (again let me emphasize,
a gene that has only been studied in mice!) can and will be used as gene therapy
for learning disabled children and/or memory diseases, such as Alzheimer's.
But where do you draw the line between slow and average and intelligent? If
learning disabled children can receive gene therapy (the idea of any gene therapy
in general borders on heavy ethical issues) why couldn't average children. Will
the therapy be an option only for the rich? The cover implies genetically altered
babies designed on parents' whims. As for memory diseases, how do we know that
this gene is the one that is part of the malfunctioning system in Alzheimer's
or Schizophrenia?

The Washington Post and New York Times reported
similar hyped themes that this gene will be available to humans for therapy.
It does seems, however, that Tang stirred the sensationalist pot by making his
statement that genetic enhancement in mammals would be feasible. The cognitive
abilities and skills of mice are far from the cognitive abilities in humans.
So where do you draw the line when reporting the potential of a gene, a gene
to enhance IQ?!

Wondering about this, I did a search and compared the sequence
alignment of the human ortholog to mouse NR2B. To view the alignment between
mouse and human NR2B, click
here. Beside the word "identities" is the percentage of nucleotides
the mouse gene and the human gene have in common. The percentage of 91% is a
very close sequence similarity. Thus the research done by Tang et .al. does
have the potential to have an impact on humans. And Tang et. al. appear
ready to jump on it; already Princeton has applied for the patent to this gene
and is talking with drug makers. This information was obtained by using the
Human-Mouse Homology
site through NCBI.

The human protein sequence for NR2B.
Below is an ideogram of human chromosome 12. The red mark indicates the location
of NR2B.

So are we headed to genetically modified intelligences? How
smart can a person be? Is there a ceiling for intellectual prowess? The potential
may be there but are the consequences too heavy? There are many controversial
questions that arise with the subject of genetic therapy...think about it.

For more popular press on "intelligence" genes I have listed a few
web sites and interesting articles.